This proposal outlines a strategy to elucidate the mechanism of function of Hox3-group genes during tissue remodeling in both normal healing and impaired healing using a diabetic mouse model. The proposed studies, focused on HoxaS, extend from our previous work on the related HoxbS and HoxdS genes which act to promote angiogenesis and wound repair. Kim's work, over the past year and a half, has shown that HoxaS is a more potent factor than HoxdS in wound repair, and that some of the cellular mechanisms which underlie this characteristic include the ability of HoxaS to induce keratinocyte migration, whereas HoxdS does not. As HoxaS appears to activate distinct target genes from HoxbS or HoxdS, Kim will investigate whether these genes are direct targets of HoxaS, as well as identify and characterize additional direct targets of HoxS-group genes during angiogenesis and wound repair using chromatin immunoprecipitation. Finally, in order to better understand the cellular pathology of impaired wound repair in the diabetic environment, Kim will test whether cytokines with established roles in wound healing normally act to induce expression of HoxS-group genes and whether the wound healing functions of these cytokines are dependent on the activation of these genes. [unreadable] [unreadable]